The goal of this proposal is to study the immune reactivity of autoimmune prone mice. We shall try to elucidate some underlying common mechanism which may contribute to the development of autoimmune disorders. Emphasis will be placed on studies of the regulation of immune responses by auto-anti-idiotypic antibody. This will be accomplished through the following specific aims: l) Studies on the kinetics of the production of auto-anti-idiotypic antibody (auto-anti-id) in the normal immune response to thymic-dependent antigens in several autoimmune prone strains of mice, 2) Analysis of the susceptibility of B cells from the NZB mouse to be inhibited by xeno anti-id, 3) Analysis of the age-related changes in the down-regulation of the immune response by auto-anti-id in the BXSB mouse and, 4) Analysis of the developmental changes at the cellular level in the regulation of auto-anti-id production in the BXSB mouse. These studies will contribute to our knowledge of the development of autoimmune diseases and the possible mechanisms leading to the increase incidence of autoantibodies in aging.